The adrenergic nervous system plays an important role at a number of levels, for example at arterial, venous, cardiac and renal level, and at the level of the central and peripheral autonomic nervous systems. Compounds capable of interacting with adrenergic receptors can thus induce a large number of physiological responses, such as vasoconstriction, vasodilation, an increase or decrease in cardiac rhythm, variation in the strength of contraction of the cardiac muscle and variation in metabolic activities. Various adrenergic compounds have been used in the past for modifying these or other physiological responses.
In addition to the fact that the compounds described in the present invention are new, they have an .alpha.2-adrenergic antagonist and monoamine reuptake-blocking profile, rendering them of use in the treatment of depression (Drug News & Perspective, 4 (4), 1991). The main problem posed by antidepressants is that they take a long time to become effective, associated with their particular manner of action. Studies have demonstrated that the association of an .alpha.2-adrenergic antagonist with an inhibitor of monoamine reuptake made it possible to reduce that length of time (Commun. Psychopharmacol, 4, pp. 95-100, 1980). The combination of those two effects in a single compound could give rise to a new generation of much more effective antidepressants. Among those compounds, napamezole (U.S. Pat. No. 5,017,584) is described as having both an .alpha.2-adrenergic antagonist activity and a monoamine reuptake-blocking activity.
The compounds of the present invention, which have new structures, have a selective .alpha.2-adrenergic antagonist profile and an ability to inhibit monoamine reuptake which is surprisingly superior to napamezole.